Basis and clinical neuroscience applications of embryonic stem cells

There have been recent dramatic advances in our understanding of the molecu lar mechanisms governing the elaboration of mature tissue-specific cellular subpopulations from embryonic stem (ES) cells, These investigations have g enerated a range of new biological and potential therapeutic reagents to al low us to dissect specific stages of mammalian development that were previo usly experimentally inaccessible, Ultimately, we will be able to reconstitu te seminal signaling pathways to promote regeneration of the nervous system , Totipotent ES cells possess an unlimited proliferative capacity that make them attractive candidates for use in a series of innovative transplantati on paradigms. Elucidation of the molecular and physiologic properties of ES cells also has important implications for our understanding of the integra tive cellular processes underlying neural induction, patterning of the neur al tube, neural lineage restriction and commitment, neuronal differentiatio n, regional neuronal subtype specification, and the specific pathological c onsequences of alterations in discrete components of these fundamental neur odevelopmental pathways, In addition, recent experimental observations sugg est that neurodegenerative disease pathology may involve alterations in a r ange of progressive neural inductive and neurodevelopmental events through novel biological mechanisms that result in sublethal impairments in cellula r homeostasis within evolving regional neuronal precursor populations conta ining the mutant proteins, culminating in increased vulnerability of their differentiated neuronal progeny to late-onset apoptosis, Future discoveries in ES cell research will offer unique conceptual and therapeutic perspecti ves that represent an alternative to neural stem cell therapeutic strategie s for ameliorating the pathologic consequences of a broad range of genetic and acquired insults to the developing, adult, and aging brain, Evolving re generative strategies for both neurodevelopmental and neurodegenerative dis eases will likely involve the targeting of vulnerable regional neural precu rsor populations during "presymptomatic" clinicopathological stages prior t o the occurrence of irrevocable neural cell injury and cell death, Anat Rec (New Anat) 265:142-156, 2001, (C) 2001 Wiley-Liss, Inc.